Objective: To assess the occurrence of dopaminergic adverse-events (AEs) in levodopa-treated Parkinson’s Disease (PD) patients that switched from entacapone (ENT) to opicapone (OPC) in the BIPARK-I open-label part.

Background: OPC, a new once-daily COMT inhibitor, has shown to be effective in the treatment of motor fluctuations in PD patients in two large, pivotal, multinational trials (BIPARK-I and II) [1,2].

Methods: After completing the BIPARK-I double-blind part, ENT-patients switched to a 1-year open-label extension, in which all subjects received OPC. This posthoc analysis investigated the occurrence of dopaminergic AEs, namely, dyskinesia, nausea, vomiting, hallucinations (including delusion, illusion and disturbance in attention), and orthostatic hypotension on those ENT ‘switchers’. Dopaminergic AEs were defined as new or worsening post-treatment from baseline or double-blind.

Results: A total of 100 patients switched from ENT to 1-year OPC open-label extension. By the end of double-blind, 4% of ENT-patients reported at least 1 dopaminergic AE. After switching to OPC, cumulatively, 22% of ENT switched-patients reported at least 1 dopaminergic AE. Most common AE was dyskinesia (20% cases) that presented an earlier onset. About 45% of ENT switched-subjects with dopaminergic AEs had a levodopa daily-dose reduction of ~25%. By the end of the 1-year OPC open-label extension, actual (by-day) frequency reported was 4% and 1%, respectively for dyskinesia and nausea. One case each of dyskinesia and orthostatic hypotension led to patient withdrawal.

Conclusions: After switching to OPC, we observed an increase in the rate of dopaminergic AEs by ENT switched-patients. This was largely due to worsening or new emergence of dyskinesia, which appeared to be controlled by levodopa reductions. These observations support an enhanced dopaminergic efficacy of OPC and an early follow-up may be warranted to perform any required levodopa adjustments in a timely manner.

References: 1. Ferreira JJ, Lees A, Rocha JF, Poewe W, Rascol O, Soares-da-Silva P, et al. Opicapone as an adjunct to levodopa in patients with Parkinson’s disease and end-of-dose motor fluctuations: a randomised, double-blind, controlled trial. Lancet Neurol 2016;15:154-165. 2. Lees AJ, Ferreira J, Rascol O, Poewe W, Rocha JF, McCrory M, et al. Opicapone as Adjunct to Levodopa Therapy in Patients With Parkinson Disease and Motor Fluctuations: A Randomized Clinical Trial. JAMA Neurol 2017;74:197-206.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/occurrence-of-dopaminergic-adverse-events-in-patients-that-switched-from-entacapone-to-opicapone-the-bipark-i-open-label-experience/